Capture Probe

ABSTRACT

A system for sampling a sample material includes a device for directing sample into a capture probe. The device for supplying sample material to the probe can be a device for radiating energy to the surface to eject sample from the sample material. A probe includes an outer probe housing having an open end. A liquid supply conduit has an outlet positioned to deliver liquid to the open end. An exhaust conduit removes liquid from the open end of the housing. The liquid supply conduit can be connectable to a liquid supply for delivering liquid at a first volumetric flow rate to the open end of the housing. A liquid exhaust system can be in fluid connection with the liquid exhaust conduit for removing liquid from the liquid exhaust conduit at a second volumetric flow rate, which exceeds the first volumetric flow rate such that gas with sample is withdrawn with the liquid. The probe can produce a vortex of liquid in the liquid exhaust conduit. A method for sampling a surface and a sampling probe system are also disclosed.

CROSS REFERENCE TO RELATED APPLICATIONS

This patent application is a continuation application of U.S.application Ser. No. 16/517,340, filed on Jul. 19, 2019, which is acontinuation application of U.S. application Ser. No. 16/108,213, filedon Aug. 22, 2018, which is a continuation application of U.S.application Ser. No. 14/682,847, filed Apr. 9, 2015, now U.S. Pat. No.10,060,838, issued on Aug. 28, 2018, and is related to Internationalapplication no. PCT/US16/26706, filed on Apr. 8, 2018, both entitled“CAPTURE PROBE”, the disclosures of which are hereby incorporated hereinfully by reference in their entireties.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH

This invention was made with government support under contract No.DE-AC05-00OR22725 awarded by the U.S. Department of Energy. Thegovernment has certain rights in this invention.

FIELD OF THE INVENTION

This invention relates generally to sample analysis systems and methods,and more particularly to sample analysis systems utilizing samplingprobes.

BACKGROUND OF THE INVENTION

The capture of sample particulates and airborne sample material provideschallenges with a liquid sampling probe, particularly in the case wheresample material is first ejected from the sample by the application ofradiant energy such as a laser beam or by acoustic desorption, orotherwise where there is a sample material that is airborne or otherwiseejected from a sample surface. The sample material if airborne candisperse before it is collected by the probe. An efficient liquid probesystem for capturing such sample material would be desirable.

SUMMARY OF THE INVENTION

A system for sampling a sample material includes a device for supplyingsample to a capture probe. The device for supplying sample material tothe probe can be a device for radiating energy to the sample material toeject sample from the sample material. The system also includes a probecomprising an outer probe housing having an inner wall and an open endfor communicating with a sample space. A liquid supply conduit isprovided within the housing and has an outlet positioned to deliverliquid to the open end of the housing. An exhaust conduit is providedwithin the housing for removing liquid from the open end of the housing.The liquid supply conduit can be connectable to a liquid supply fordelivering liquid at a first volumetric flow rate to the open end of thehousing. A liquid exhaust system can be in fluid connection with theliquid exhaust conduit for removing liquid from the liquid exhaustconduit at a second volumetric flow rate. The second volumetric flowrate exceeds the first volumetric flow rate, whereby gas containingsample from the sample space will be withdrawn with liquid flowingthrough the liquid exhaust conduit. The probe can produce a vortex ofliquid in the liquid exhaust conduit.

The device for radiating energy can be a laser producing a laser beam.The sample can be provided on a support that is transparent to thewavelength and the laser can be positioned to direct the laser beamthrough the support to the sample. The laser can be positioned on thesame side of the support as the sample.

The second volumetric flow rate can exceed the first volumetric flowrate by at least 5%. The second volumetric flow rate can exceed thefirst volumetric flow rate by between 5-50%.

The system can further include a gas guide between the open end of theprobe and the sample material for focusing the flow of gas into theliquid exhaust conduit.

A voltage source can be electrically connected to create a voltagedifference between the sample material and the probe.

A method for sampling a sample material can include the step ofproviding a device for directing sample into a capture probe. The samplematerial can be positioned on a sample support. A radiation energysource can be provided for directing a beam of radiation at the samplematerial. A probe is provided having an open end. The open end can bepositioned a distance from the sample and the sample support to define asample space. Liquid can be supplied to the open end of the probe at afirst volumetric flow rate. The liquid can be removed from the open endof the probe at a second volumetric flow rate, the second volumetricflow rate exceeding the first volumetric flow rate. The radiation energysource can be operated to eject sample material from the sample. Theejected sample material and gas from the sample space can be removedwith the liquid removed from the open end of the probe. The removedliquid containing sample and gas can be subjected to chemical analysis.The liquid removed from the open end can form a vortex as it enters aliquid exhaust conduit.

The radiation energy can be a laser beam. The sample can be provided ona support that is transparent to the wavelength and the laser can bepositioned to direct the laser beam through the support to the sample.The laser beam can emanate from the same side of the support as thesample.

The second volumetric flow rate can exceed the first volumetric flowrate by at least 5%. The second volumetric flow rate can exceed thefirst volumetric flow rate by between 5-50%.

The method can further include the step of providing a gas guide betweenthe open end of the probe and the sample for focusing the flow of gas inthe sample space and into the liquid exhaust conduit.

The method can further include the step of creating a voltage differencebetween the sample and the probe.

A sampling probe system can include an outer probe housing having aninner wall and an open end for communicating with a sample space, aliquid supply conduit within the housing and having an outlet positionedto deliver liquid to the open end of the housing, and an exhaust conduitwithin the housing for removing liquid from the open end of the housing.The liquid supply conduit can be connectable to a liquid supply fordelivering liquid at a first volumetric flow rate to the open end of thehousing. A liquid removal system can be in fluid connection with theliquid exhaust conduit for removing liquid from the liquid exhaustconduit at a second volumetric flow rate. The second volumetric flowrate exceeds the first volumetric flow rate, whereby gas containingsample from the sample space will be withdrawn with liquid flowingthrough the liquid exhaust conduit. The liquid can enter the liquidexhaust conduit as a vortex.

BRIEF DESCRIPTION OF THE DRAWINGS

There are shown in the drawings embodiments that are presently preferredit being understood that the invention is not limited to thearrangements and instrumentalities shown, wherein:

FIG. 1 is a schematic diagram of a system for sampling a surface.

FIG. 2B is an enlarged schematic diagram of area A in FIG. 1. FIG. 2A isan enlarged schematic diagram of area B in FIG. 2.

FIG. 3A is a plot of Rel. Area (%) vs. Probe-to-surface Distance (mm);and FIG. 3B a schematic diagram illustrating the distance h of the probeto the sample.

FIG. 4A is a plot of Rel. Area (%) vs. Probe Offset from Vertical CenterLine (mm); and FIG. 4B a schematic diagram illustrating the position xof the probe from the center line.

FIGS. 5A-5C are plots of mass to charge (m/z) ratio vs. Rel. Int. (%)for FIG. 5A polypropylene glycol; FIG. 5B bovine insulin side chain B;and FIG. 5C horse heart cytochrome c.

FIG. 6A is a chemical structure diagram of the dye basic blue 7, presentin blue permanent marker ink; FIG. 6B is a schematic diagramillustrating the oversampling methodology; FIG. 6C is an optical imageof stamped blue ink grid pattern; and FIG. 6D is a chemical image ofbasic blue 7 from the same stamped ink pattern.

FIG. 7A is a chemical structure diagram of phosphatidylcholine lipid;FIG. 7B is an optical image of a portion of a small animal brain thinsection; and FIG. 7C is a chemical image of the phosphatidylcholinelipid from the same portion of the thin section.

FIG. 8A is a chemical structure diagram of raclopride; FIG. 8B is anoptical image of a small animal brain thin section; FIG. 8C is anenlarged optical image of the thin section; and FIG. 8D is a chemicalimage of raclopride from the same portion of the thin section.

FIG. 9A is a chemical structure diagram for Novolac resin; FIG. 9B is anoptical image of a photoresist pattern formed from Novolac resin; andFIG. 9C is a chemical image of the chemical components of the Novolacresin from the same portion of the photoresist pattern.

FIG. 10A is a chemical structure for Novolac resin; FIG. 10B is anoptical image for a second photoresist pattern formed from Novolacresin; and FIG. 10C is a chemical image of the chemical components ofthe Novolac resin from the same portion of the this second photoresistpattern.

FIG. 11 is a schematic diagram of a probe with vortex liquid flow.

FIG. 12 is a schematic diagram of a probe with plume-focusing gas flow.

FIG. 13 is a diagram illustrating computer model results for gas flowinto the exhaust conduit of a probe.

FIG. 14A is a schematic diagram of a system with a plume-focusing gasguide spaced between the sample support and the probe; FIG. 14B is across section of the gas guide in a first focusing gas flow portconfiguration; and FIG. 14C is a cross section of the gas guide in asecond focusing gas flow port configuration.

FIG. 15A is a schematic diagram of a system with a plume-focusing gasguide in a baffle configuration; and FIG. 15B is a cross section of thegas guide.

FIG. 16A is a cross section of a plume-focusing gas guide; FIG. 16B is avertical cross section; FIG. 16C is a no plume-gas focusing guide; FIG.16D is a gas guide having first height h; FIG. 16E is a gas guide havinga second height h′; and FIG. 16F is a gas guide having a third heighth″.

FIG. 17A is a schematic diagram of a system with a plume-focusing gasguide that is separated from the sample support; and FIG. 17B is a crosssection of the gas guide.

FIG. 18A is a cross section of a plume-focusing gas guide that isdetached from the sample support; FIG. 18B is a schematic diagramillustrating guide wall height; schematic diagrams of FIG. 18C is a noplume-gas focusing guide; FIG. 18D is a gas guide having first height h;FIG. 18E is a gas guide having a second height h′; and FIG. 18F a gasguide having a third height h″.

FIG. 19 is a schematic diagram of a system enabling a voltage differenceto be applied between the sample and probe.

FIG. 20A is a schematic diagram of a system for sampling a surface; FIG.20B is an enlarged area B; and FIG. 20C is a depiction of liquid and gasflow into the probe.

FIG. 21 is a schematic diagram of a droplet dispenser for supplyingsample to the probe.

DETAILED DESCRIPTION OF THE INVENTION

FIG. 1-2 are schematic diagrams of a system for sampling a surface.There is shown in the figures a system 20 for sampling a sample area 32including a sample surface 96 which includes a device 28 for radiatingenergy to the surface 96 to eject sample from the sample material. Theinvention can be utilized with many different systems and methods forgenerating sample material and directing the sample material into ortoward the probe. The probe is shown in a vertical orientation, but canalso be used in other orientations. The system also includes a probe 39comprising an outer probe housing 40 having an inner wall 41 and an openend 42 for communicating with a sample space 104. A liquid supplyconduit 43 is provided within the housing and has an outlet positionedto deliver liquid to the open end of the housing. An exhaust conduit 52is provided within the housing 40 for removing liquid from the open end68 of the exhaust conduit 52. The position of the open end 68 relativeto the open end 42 of the probe can vary to adjust flow conditions intothe exhaust conduit 52. The liquid supply conduit can be an annularspace between the exhaust conduit 52 and the inner wall 41 of thehousing 40. Other configurations are possible for delivering solvent tothe open end of the housing, for example, one or more tubular liquidsupply conduits.

The liquid supply conduit can be connectable to a liquid supply such asintake line 72 for delivering liquid as shown by arrow 56 at a firstvolumetric flow rate to the open end 42 of the housing 40. A liquidexhaust system can be in fluid connection with the liquid exhaustconduit 52 for removing liquid as shown by arrow 60 from the liquidexhaust conduit 52 at a second volumetric flow rate. The secondvolumetric flow rate exceeds the first volumetric flow rate, whereby gascontaining sample from the sample space 104 will be withdrawn withliquid flowing through the liquid exhaust conduit 52. The probe 39 canproduce a vortex 45 of liquid in the liquid exhaust conduit 52 as shown,although a vortex is not necessary for functioning of the device. Therelative diameters of the liquid exhaust conduit 52 di, the liquidsupply conduit 43 d₂ and the outer diameter of the probe 39 d₃ can vary.The distance between the sample and liquid surface 64 can vary, asindicated by the arrows h in FIG. 2A.The distance from the inlet of theliquid exhaust conduit 52 and the open end 42 of the housing 40 can alsovary.

The excess of volume leaving the liquid exhaust conduit 52 at the secondvolumetric flow rate relative to the amount of liquid entering the probeat the first volumetric flow rate results at the entrance to the liquidexhaust conduit 52 in the draw of gas from the sample space 104 into theliquid exhaust conduit 52. Positioning of the open end 42 below thesample 96 at the point where radiant energy strikes the sample 96 willcause sample material to fall or otherwise be ejected toward the liquidsurface 64. Liquid including the captured sample material will enter theliquid exhaust conduit 52 and thereby collected for further analysis.Airborne sample material ejected from the sample will be assisted to thecenter of the liquid exhaust conduit 52 by gas flow created by thegreater volumetric flow of liquid out of the probe 39 through theexhaust conduit 52 than into the probe 39 through the supply conduit 43.

The amount by which the second volumetric flow rate exceeds the firstvolumetric flow rate can vary, and will in part depend upon thecharacteristics of the sample, liquid, and probe size and geometry. Inone embodiment, the second volumetric flow rate can exceed the firstvolumetric flow rate by at least 5%. In another embodiment the secondvolumetric flow rate can exceed the first volumetric flow rate bybetween 5-50%.

The device 28 for directing sample into the capture probe 39 can be alaser radiating energy such as a laser beam 92. The device for radiatingenergy can radiate intense heat. The wavelength and intensity of theenergy can vary based upon the characteristics of the sample beingtested. The sample 96 can be provided on a support 100. The support 100can be transparent to the wavelength of the radiated energy such thatthe laser 28 can be positioned to direct the laser beam 92 through thesupport to the sample 96. The laser 28 can be positioned on the sameside of the support 100 as the sample 96 such that a laser beam 93emanates directly at the sample 96 without passing through the support100. The device for directing sample into the capture probe can be anacoustic desorption device wherein a laser or other energy impartingdevice is used to generate an acoustic wave which travels through thesample support to impart energy to the sample and eject sample materialfrom the sample. The acoustic desorption can be laser induced acousticdesorption. The invention can be used with other means for ejectingsample material from the sample to the probe, and many other devices andmethods for directing sample into the capture probe.

The system 20 can deliver to and remove solvent from the probe 39 by anysuitable means. The liquid intake line 72 receives liquid from asuitable source such as a container or a liquid supply line. A pump suchas an HPLC pump (not shown) can be used to meter solvent flow into theprobe 39. The liquid can be any suitable solvent for the samplematerial, such as water, methanol, or acetonitrile. Other solvents arepossible. A T-connection 76 can include a fitting 78 to engage the probe39 and make a fluid connection with fitting 79 and between the liquidsupply line 72 and the liquid supply conduit 43. A fitting 80 can make aconnection between the liquid exhaust conduit 52 and the liquid exhaustline 86. The exhaust line 86 can be connected to inlet 120 of a chemicalanalysis device such as a mass spectrometer. Other connection materialsand methods are possible.

The system 20 can have other features. A 90 degree prism 88 can beprovided to direct the laser beam through a microscope objective 84. Alight source 108 can be provided. A video monitor 116 can be provided. Amass spectrometer 124 or other chemical analysis device can be providedand can have a monitor 128 and a suitable control 132 joystick or othercontrol device.

FIG. 3 is FIG. 3A a plot of Rel. Area (%) vs. Probe-to-surface Distance(mm); and FIG. 3B a schematic diagram illustrating the distance h of theprobe to the sample. FIG. 3A illustrates that capture of materialejected from the surface is relatively constant to a 1.5 mm spacing.

FIG. 4 is FIG. 4A a plot of Rel. Area (%) vs. Probe Offset from VerticalCenter Line (mm); and FIG. 4B a schematic diagram illustrating theposition x of the probe from the center line. The plot of FIG. 4Aillustrates that capture of material ejected from the surface isrelatively stable with probe movement illustrated by arrow x in FIG. 4Bup to 1 mm from the vertical center line. In this embodiment gravityhelps to direct ablated material down towards the capture liquid.

FIG. 5 is a plot of mass to charge (m/z) vs. Rel. Int. (%) for FIG. 5Apolypropylene glycol; FIG. 5B bovine insulin side chain B; and FIG. 5Chorse heart cytochrome c obtained using positive ion mode electrosprayionization mass spectrometry for detection. FIG. 5A is the result of theanalysis of a propylene glycol mixture containing PPG 425-0.1 nmolespotted on a Director® slide. The capture solvent was 80/20/0.1 (v/v/v)methanol/water/formic acid at 200 μL/min. FIG. 5B is the result for theanalysis of bovine insulin side chain B (3494 Da)-0.3 nmol spotted on aDirector® slide. The capture solvent was 50/50/0.1 (v/v/v)acetonitrile/water/formic acid flowing at 200 μL/min. FIG. 5C is theresult for horse heart cytochrome c (12360.2 Da)-81 pmol spotted on aDirector® slide. These mass spectra illustrate that with this system awide variety of organic and biological molecules can be ejected from thesurface using a laser, captured in a liquid, ionized and mass analyzed,with the molecules remaining intact.

Testing of the chemical imaging capability of this system was performedusing a stamped ink grid containing the dye basic blue 7 (m/z 478 havingthe chemical structure shown in FIG. 6A). There is shown in FIG. 6B aschematic diagram illustrating a sampling methodology termedoversampling, where the laser spot 180 is scanned over an incrementalstep 188 on ink line 184 in the direction of arrow 192 leaving a sampledarea 196. The laser spot size d was 50 μm, the surface scan speed 10μm/s, with 2.5 μm steps between lanes and 51 lane scans. Capture liquidflow was methanol+0.1% formic acid at 200 μL/min. Analysis was performedwith AB Sciex Triple TOF 5600+, full scan m/z 100-1000 using positiveion mode electrospray ionization, 250 ms acquisition time. A 355 nmNd:YAG laser was used at 10 Hz, 60 μJ/pulse. The chemical image shown inFIG. 6D correlates well with the optical image shown in FIG. 6C. Thepixel size was 2.5 μm×2.5 μm.

There is shown in FIG. 7A a chemical structure diagram of thephosphatidylcholine lipid from mouse brain detected using a selectedreaction monitoring tandem mass spectrometry mode to improve detectionselectivity. The mouse brain tissue was placed on a PEN 1.0 slide. Thelaser spot was 50 μm. The acquisition parameters were 50 μm/s and 20 μmsteps with 151 lanes. Solvent flow was 200 μL/min, methanol+0.1% formicacid. Analysis was performed with AB Sciex Triple TOF 5600+, usingpositive ion mode electrospray ionization product ion m/z 760.6→184.06(CE=45 eV), 250 ms acquisition time. A 355 nm Nd:YAG laser was used at10 Hz, 60 μJ/pulse. The chemical image shown in FIG. 7C correlates wellwith the optical image shown in FIG. 7B. The image pixel size was 12μm×20 μm.

There is shown in FIG. 8A a chemical structure diagram of raclopride.Raclopride has a high affinity for dopamine D-2 receptors in rat brain.Rats were IV-dosed with 2 mg/kg raclopride and sacrificed 5 minutes postdose. The excised brain was flash frozen, sectioned at 6 μm thick, andthaw mounted on PEN 1.0 slides. The imaging was performed on 9 μm×10 μmpixels, with a 12×10 μm laser spot. The acquisition parameters were 40μm/s and 10 μm steps with 151 lanes. Solvent flow was 200 μL/min,methanol+0.1% formic acid. Analysis was performed with AB Sciex TripleTOF 5600+, using positive ion mode electrospray ionization and selectedreaction monitoring m/z 347.1→112 (CE=45 eV), 250 ms acquisition time. A355 nm Nd:YAG laser was used at 10 Hz, 60 μJ/pulse. The chemical imageshown in FIG. 8D correlates well with the optical image shown in FIG.8C.

There is shown in FIG. 9A a chemical structure diagram for Novolacresin, having a 120 Da monomer unit. The experiment was performed onNovolac resin developed positive photoresist (1.5 μm thick) on glass. A355 nm Nd:YAG laser was used at 10 Hz, 25 μJ/pulse. Analysis wasperformed by AB Sciex 5500 using negative ion mode electrosprayionization and selected reaction monitoring (m/z 227.2→107.2 (CE=30 eV),50 ms dwell time). The surface scan speed was 6.7 μm/s, with 2.5 μm/lanestep and 17 μm ablation spot. Solvent flow was 200 μL/min methanol. Thetotal acquisition time was 4.5 h. The chemical image shown if FIG. 9Ccorrelates well with the optical image shown in FIG. 9B. The pixel sizewas 2.5 μm×2.5 μm.

There is shown in FIG. 10A the chemical structure for Novolac resin;Solvent flow was 200 μL/min methanol. A 355 nm Nd:YAG laser was used at10 Hz, 25 μJ/pulse. Analysis was performed by AB Sciex 5500 usingnegative ion mode electrospray ionization and selected reactionmonitoring (m/z 227.2→107.2 (CE=30 eV), 50 ms dwell time). The scanspeed was 6.7 μm/s, with 0.5 μm/lane step and 17 μm ablation spot.Solvent flow was 200 μL/min methanol. The total acquisition time was 2h. The chemical image shown in FIG. 10C correlates well with the opticalimage shown in FIG. 10B. The pixel size was 0.5 μm×0.5 μm.

FIG. 11 is a schematic diagram of a probe and liquid vortex within.Liquid supplied through the liquid supply conduit 43 forms a liquidsurface 64 at the open end of the probe 40. The liquid surface 64captures sample material that has been ejected from the sample by theradiant energy or other sample introduction method. The over aspirationof liquid through the liquid exhaust conduit 52 relative to thevolumetric flow rate of liquid through the liquid supply conduit 43draws gas containing airborne sample material from space 68 into theliquid exhaust conduit. Depending on the liquid flow and geometry avortex 45 can be formed by liquid flowing into the liquid exhaustconduit.

FIG. 12 is a schematic diagram of a probe with plume-focusing gas flow.Radiant energy such as laser beam 92 in transmission mode, or beam 160in reflection mode from the same side of the support 100 as is thesample 96, strikes the sample 96 and creates a plume 178 of ejectedsample material, which can be particulates, gaseous species or otherairborne material. Gas flow 182 drawn from the ambient environment bythe probe flows generally radially inward toward the plume 178 to focusthe plume and direct particulates and gas into the surface 64 and intothe liquid exhaust conduit 52 in the direction of arrow 48. The precisedirection and extent of focusing gas flow can vary depending on systemgeometry and operating characteristics. The ambient focusing gas can beair or another gas. FIG. 13 is a diagram illustrating computer modelresults for focusing gas flow 198 into the modeled exhaust conduit 204of a probe 202. The model illustrates how the focusing gas guides thesample plume into a center space 203 and then into the exhaust conduit204.

FIG. 14A is a schematic diagram of a system with a plume-focusing gasguide 232 spaced between the probe 40 and sample support 100. The gasguide 232 has a series of apertures 233 to direct focusing gas flow 234radially inward. FIG. 14B is a cross section of the gas guide 232showing the radially inward focusing gas flow 234. FIG. 14C is a crosssection of an alternative gas guide 238 in a second focusing gas flowport configuration in which more tangentially oriented guide ports 239are provided and direct focusing gas flow 240 in a cyclonic pattern soas to create gas vortex 242.

FIG. 15A-15B is a schematic diagram of a system with a plume-focusinggas guide 280 in a baffle configuration and connected to the support100. Focusing gas 284 flows under the baffle guide 280 where it contactsthe support 100 and is directed radially inward as illustrated by arrows294.

FIG. 16A-16F illustrates a plume-focusing gas guide baffle 290 with avariety of heights. FIG. 16C illustrates the case of no baffle guide,and FIG. 16D-16F illustrates baffles guides 290, 290′, and 290″ whichhave a respectively greater height h.

FIG. 17A-17B a schematic diagram of a system with a plume-focusing gasguide 320 that is separated from the sample support 100. The detachedposition of the gas guide 320 creates a circumferential channel 324through which radially inwardly directed focusing gas flow 328 can pass,where it moves in flow 332 toward the liquid exhaust conduit 52. FIG.18A-18F illustrates the plume-focusing gas guide 320 at a variety ofdifferent heights h, including the case with no gas guide.

FIG. 19 is a schematic diagram of a system with a voltage-applyingsource 340 and electrical connections 344 to the support 100 and 348 tothe probe 39. The application of a voltage difference will assist in thetransport of charged components in the plume 178 to the probe 39. Thevoltage difference that can be applied can vary.

FIG. 20A is a schematic diagram of a system 400 for sampling a surface.The system 400 has a base unit 402 having a probe 39 and liquid supplyand exhaust assembly as previously describe and illustrated by area Cand FIG. 20B. A camera 112 and eyepiece 412 can be provided. A UV shield416 can also be provided. A commercial laser microdissection system suchas the LMD 7000 from Leica can be used and has an optical bright fieldand fluorescent microscope in addition to laser ablation capability.Other systems and configurations are possible to generate sample anddirect it toward and into the probe. FIG. 20C illustrates vortex flow atthe open end of the probe.

It is possible to direct sample into the capture probe by means otherthan ejecting the sample from a sample material. There is shown in FIG.21A a schematic diagram of a droplet dispenser 430 for supplying sampleto the probe 39. The droplet dispenser can contain solvent and samplefrom any source, and can be oriented in any direction to direct dropletsinto or toward the probe by any suitable means. The droplets 434 can besized by the flow rate and orifice diameter of the droplet dispenser 430such that the diameter of the droplets 434 can be less than the diameterof the liquid exhaust conduit 52 and can be dispensed directly into theliquid exhaust conduit 52. Gas flow 444 into the exhaust conduit guidesthe sample droplets 442 into the liquid exhaust conduit 52.

A method for sampling a surface can include the step of directing sampleinto a capture probe. The directing step can include the step ofproviding a sample support for retaining a sample. A device such as aradiation energy source, an acoustic ablation source, or a dropletdispenser can be provided for directing sample into the probe, forexample by a beam of radiation striking the sample such that sample isejected into the probe. A probe is provided having an open end. The openend can be positioned a distance from the sample and the sample supportto define a sample space. Liquid can be supplied to the open end of theprobe at a first volumetric flow rate. The liquid can be removed fromthe open end of the probe at a second volumetric flow rate, the secondvolumetric flow rate exceeding the first volumetric flow rate. Theradiation energy source can be operated to eject sample material fromthe sample. The ejected sample material and gas from the sample spacecan be removed with the liquid removed from the open end of the probe.The removed liquid containing sample and gas can be subjected tochemical analysis. The liquid removed from the open end can form avortex. The method can further include the step of providing a gas guidebetween the open end of the probe and the sample for focusing the flowof gas into the liquid exhaust conduit. The method can further includethe step of creating a voltage difference between the sample and theprobe.

The method can further include the step of performing chemical analysison liquid drawn into and passing through the exhaust conduit. Thechemical analysis device can be at least one selected from the groupconsisting of high performance liquid chromatography and massspectrometry. The analytical instrument for example can be anyinstrument utilized for analyzing analyte solutions. Exemplaryanalytical instruments include, but are not limited to, massspectrometers, ionization sources, spectroscopy devices, separationmethods, and combinations thereof. Exemplary ionization sources include,but are not limited to electrospray ionization (ESI), atmosphericpressure chemical ionization (APCI) , electrospray chemical ionization(ESCi), atmospheric pressure photo-ionization (APPI) or inductivelycoupled plasma (ICP). Exemplary separation methods include, but are notlimited to liquid chromatography, solid phase extraction, HPLC,capillary electrophoresis, or any other liquid phase sample cleanup orseparation process. Exemplary mass spectrometers include, but are notlimited to, sector time-of-flight, quadrupole mass filterthree-dimensional quadrupole ion trap, linear quadrupole ion trap,Fourier transform ion cyclotron resonance orbitrap and toroidal iontrap.

A processor 404 shown in FIG. 20 can be provided to control operation ofthe device, and particularly the flow rates of the liquid supply, liquidexhaust and vortex as desired. The processor can also control theoperation of the sample-supplying device such as the laser 200. Theprocessor can receive sensor signals and provide control signals tosuitable valves and control circuitry to control operation of thesedevices and the system in general.

The system of the invention can also be operated in an overflow mode inwhich the first volumetric flow rate exceeds the second volumetric flowrate. Such a system is described in a copending United States patentapplication entitled “Open Port Sampling Interface” filed on even dateherewith, the disclosure of which is hereby fully incorporated byreference.

Ranges: throughout this disclosure, various aspects of the invention canbe presented in a range format. It should be understood that thedescription in the range format is merely for convenience and brevityand should not be construed as an inflexible limitation on the scope ofthe invention. Accordingly, the description of a range should beconsidered to have specifically disclosed all the possible subranges aswell as individual numerical values within that range. For example,description of a range such as from 1 to 6 should be considered to havespecifically disclosed subranges such as from 1 to 3, from 1 to 4, from1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well asindividual numbers within that range for example, 1, 2, 2.7, 3, 4, 5,5.3 and 6. This applies regardless of the breadth of the range.

This invention can be embodied in other forms without departing from thespirit or essential attributes thereof, and accordingly, referenceshould be had to the following claims to determine the scope of theinvention.

1. A method of sampling a surface of a sample for analysis, comprising:positioning an open end of a capture probe opposite the sample and inalignment with a device for directing sample into the capture probe;supplying capture liquid to an open end of the capture probe andremoving the supplied capture liquid from the open end through a liquidexhaust conduit; imparting radiating energy through the sample using thedevice for directing sample to eject sample material from the surface ofthe sample towards the open end of the capture probe; capturing theejected sample material with the capture liquid flowing through theliquid exhaust conduit at the open end of the capture probe; removingthe capture liquid and the captured sample material from the open end ofthe capture probe; and, directing the capture liquid and the samplematerial towards an inlet of a chemical analysis device.
 2. The methodof claim 1, wherein the sample is provided on a support that istransparent to the radiated energy and located between the sample andthe device for directing sample, and wherein the radiated energy isdirected by the device for directing sample through the support and intothe sample.
 3. The method of claim 2, wherein the radiating energycomprises a laser beam that generates an acoustic wave in the sample. 4.The method of claim 2, wherein the device for directing sample comprisesan acoustic desorption device, and wherein the radiating energy directedthrough the support comprises an acoustic wave which travels through thesupport to impart energy into the sample and to eject the samplematerial from the sample.
 5. The method of claim 1, wherein the captureprobe is located below the sample, and wherein gravity helps to directejected sample material into the capture liquid.
 6. The method of claim1, further comprising directing a gas flow radially inward towards theopen end of the capture probe to direct the ejected sample material intothe capture liquid.
 7. The method of claim 1, wherein the capturing theejected sample material with capture liquid further comprises drawinggas containing airborne sample material into the capture liquid.
 8. Themethod of claim 1, wherein a liquid surface of the capture liquid thatcaptures the sample material extends into the liquid exhaust conduit. 9.The method of claim 1, wherein the positioning an open end of a captureprobe opposite the sample further comprises locating an open end of theliquid exhaust conduit to a position opposite the device for directingsample and aligned with a location of sample ejection from the samplesuch that sample material ejected from the sample is directed into thecapture liquid at the open end of the liquid exhaust conduit.
 10. Themethod of claim 1, wherein the ejected sample material comprises aportion of the sample released from the surface of the sample with themolecules remaining intact.
 11. A system for sampling a surface of asample for analysis, comprising: a capture probe including a liquidsupply conduit for supplying a capture liquid to an open end of theprobe and a liquid exhaust conduit for removing the capture liquid fromthe open end of the probe and directing the removed capture liquid andany captured sample material to a chemical analysis device; a device fordirecting sample operative to direct radiating energy through the sampleto impart energy to the sample and to eject the sample material from thesurface of the sample towards the open end of the capture probe; whereinthe open end of the capture probe may be positioned opposite the surfaceof the sample and in alignment with the device for directing sample intothe sample such that when the device for directing sample is energized,radiating energy is directed through the sample to impart energy to thesample and to eject sample material from the surface of the sampletowards the open end of the capture probe for capture in capture liquidwithin the liquid exhaust conduit.
 12. The system of claim 11, forsampling a surface of a sample for analysis, further comprising: asample support for retaining the sample, the sample support transparentto radiating energy, and wherein the sample support is located betweenthe sample and the device for directing sample such that the radiatingenergy generated by the device for directing sample travels through thesample support to impart energy to the sample and eject sample materialfrom the sample.
 13. The system of claim 11, wherein the radiatingenergy comprises a laser beam that generates an acoustic wave in thesample.
 14. The system of claim 11, wherein the device for directingsample comprises an acoustic desorption device, and wherein theradiating energy directed through the support comprises an acoustic wavewhich travels through the support to impart energy into the sample andto eject the sample material from the sample.
 15. The system of claim11, wherein the capture probe is located below the sample, and whereingravity helps to direct ejected sample material into the capture liquid.16. The system of claim 11, further comprising directing a gas guideoperative to direct a gas flow radially inward from the sample towardsthe open end of the capture probe to direct the ejected sample materialinto the capture liquid.
 17. The system of claim 11, wherein the captureprobe is operative to over aspirate the capture liquid through theliquid exhaust conduit to draw gas containing airborne ejected samplematerial into the liquid exhaust conduit for capture by the captureliquid.
 18. The system of claim 11, wherein the open end of the captureprobe is further positioned to locate an open end of the liquid exhaustconduit of the capture probe opposite the device for directing sampleand aligned with a location of sample ejection from the sample such thatsample material ejected from the sample is directed into the captureliquid at the open end of the liquid exhaust conduit.
 19. The system ofclaim 11, wherein the chemical analysis device comprises a massspectrometer, operative to ionize and mass analyze the removed captureliquid and captured sample material.
 20. The system of claim 11, furthercomprising: a processer operative to control flow rates of the captureliquid to the open end of the probe, removal of the capture liquid fromthe open end of the probe, and/or operation of the device for ejectingsample.
 21. The system of claim 11, wherein the ejected sample materialcomprises a portion of the sample released from the surface of thesample with the molecules remaining intact.